Archive for the ‘TROPICAL DISEASES’ Category

London: An Australian company has won unprecedented US approval for a new drug to treat the second most common preventable cause of blindness in the world.

In the process, Medicines Development for Global Health, based in Melbourne, became the first not-for-profit company in the world to register a medicine with the US Food and Drug Administration.

Mark Sullivan, managing director of Medicines Development for Global Health.

Photo: Supplied

The World Health Organisation has been calling for better treatments for river blindness for more than a decade, but because the medicine would be mostly used by those in poverty-stricken countries, there has been no financial incentive for drug companies to develop new treatments. The current treatment is 20 years old.

River blindness is caused by parasitic worms and spread by black flies. It affects the skin and eyes and is prevalent in sub-Saharan Africa.

In a double-win for Medicines Development for Global Health, it has also won a highly sought after voucher designed to financially reward companies that develop drugs for neglected diseases.

Managing director Mark Sullivan said while FDA approval for the company’s drug, moxidectin, was a “momentous achievement” for any pharma company, it was “a particularly rare and exciting event” for those trying to treat neglected diseases.

The FDA gave its approval for the treatment, which is swallowed as a tablet, in June after the application was submitted in October 2017.

Mr Sullivan established the Melbourne-based not-for-profit company in 2005 with the sole purpose of filling the gap left by the big pharmaceutical companies by developing medicines that were based on need for treatment rather than the patients’ ability to afford them.

Medicines Development for Global Health has been working for five years on the development of the drug and is now planning to develop moxidectin as a new treatment for scabies, a common problem in Indigenous communities.

Priority review voucher

The company has also won a priority review voucher under a scheme set up in 2007 to create a financial incentive to reward drug makers willing to spend the time and money developing treatments for the some of the world’s most neglected diseases. The scheme creates a market for making new drugs that the private market was not filling itself.

Under the scheme, a company that wins a voucher gets a fast track through the FDA for consideration of its next new drug, even if it’s a treatment that would have a commercial return. This gives it a head-start over its rivals.

Crucially, a company can also on-sell the voucher to a bigger company willing to pay anywhere between $US100 million and $300 million for the right to almost halve the approval time.

Because Medicines Development for Global Health is a not-for-profit, its proceeds from drug sales and the voucher will be reinvested in the company to develop new drugs & medications for other neglected diseases.

“Our plan is to sell the voucher and use the funds to support further development of moxidectin for other neglected diseases but also to expand our portfolio into other medicines and vaccines,” Mr Sullivan said.

Professor David Ridely from Duke University authored the scheme and said Medicines Development for Global Health was a textbook example of how he envisaged the program would work.

“I’m delighted that the voucher program is playing a role in treating patients with river blindness, and one day eliminating the disease,” he said.

Mr Sullivan said the development of moxidectin could not have been possible without a $US13 million co-investment from the Global Health Investment Fund, which is the social impact investment fund initially put together by the Bill and Melinda Gates Foundation.

”We believe moxidectin may play a pivotal role in eventually eradicating river blindness, and look forward to working with MDGH and others in making this happen,” Curt LaBelle, managing partner at the investment fund, said.

Color-enhanced Scanning Electron Micrograph (SEM) of Onchocerca volvulus, image of a female worm with microfilaria. O. volvulus is a nematode that causes onchocerciasis, or “river blindness,” mostly in Africa. Long-term corneal inflammation, or keratitis, leads to thickening of the corneal stroma which ultimately leads to blindness.

The Food and Drug Administration (FDA) has approved moxidectin for the treatment of onchocerciasis (river blindness) due to Onchocerca volvulus in patients ≥12 years of age.

Moxidectin, a macrocyclic lactone, is an anthelmintic drug that selectively binds to the parasite’s glutamate-gated chloride ion channels. It is active against O. volvulus microfilariae but it does not kill adult O. volvulus parasites. The tropical disease spreads from person to person via black flies that breed near rivers in South and Central America, sub-Saharan Africa and Yemen

Weathers has made several high-producing versions of the plant using tissue cultures (Credit: Worcester Polytechnic Institute)

When 18 malaria patients in the Congo failed to respond to conventional treatments and instead continued to head toward terminal status, doctors knew they had to act fast – and try something different. So instead of turning to more synthetic drugs, they turned instead to nature and found a solution that delivered remarkable results.

The patients were first treated with the regimen described by the World Health Organization (WHO): artemisinin-based combination therapy (ACT). This drug combines an extract from a plant known as Artemisia annua, with other drugs that launch a multi-pronged attack on the malaria parasite. But just as is the case with antibiotic-resistant bacteria, the malaria parasite is evolving to resist the drugs designed to kill it. In fact, according to the WHO, three of the five malarial parasites that infect humans have shown drug resistance.

As the patients continued to decline, with one five-year-old even entering into a coma, the doctors administered a drug called artesunate intravenously, which is the preferred course of action when treating severe malaria. The treatment didn’t work.

Finally, doctors turned to the Artemisia annua plant itself. Also called sweet wormwood or sweet Annie, the plant is the source of the chemical artemisinin, which is used in ACT therapy. The plant has been used since ancient times in Chinese medicine to treat fevers, although this bit of knowledge was lost until 1970 when the Chinese Handbook of Prescriptions for Emergency Treatments (340 AD) was rediscovered. In 1971 it was found that extracts from the plant could fight malaria in primates.

Pamela Weathers, professor of biology and biotechnology at Worcester Polytechnic Institute began researching Artemisia annua over 25 years ago. Along with postdoctoral fellow Melissa Towler, Weathers created a pill made from nothing more than the dried and powdered leaves of the plant. When the pills were given to the 18 dying patients over the course of five days, all of them completely recovered, with no trace of the malaria parasite remaining in their blood.

“These 18 patients were dying,” Weathers said. “So to see 100 percent recover, even the child who had lapsed into a coma, was just amazing. It’s a small study, but the results are powerful.”

Weathers had previously shown that the dried leaves of the Artemisia annua plant (DLA) could deliver 40 times more Artemisia annua to the blood than extracts of the plant alone. In a later experiment, she showed that not only could the leaves beat drug-resistant bacteria in mice, but that after passing the malaria parasite through 49 generations of mice, the parasite still showed no resistance to the plant.

While the exact mechanism through which DLA operates is unclear, Weathers says it’s likely due to the intricate chemical dance that occurs between the phytochemicals in the leaves.

Because the drug is inexpensive and relatively simply to produce, Weathers also says that it could be a source of industry for people living in the areas where malaria is a problem, such as Ghana, Kenya and Malawi where it was recently announced that the first malaria vaccines will be deployed. “This simple technology can be owned, operated, and distributed by Africans for Africans,” said Weathers, who has already established a supply chain on the continent for the leaves using local producers.

Weathers also said that further research into DLA could lead to effective ways to combat other maladies.

“We have done a lot of work to understand the biochemistry of these compounds, which include a number of flavonoids and terpenes, so we can better understand the role they play in the pharmacological activity of the dried leaves,” Weathers said. “The more we learn, the more excited we become about the potential for DLA to be the medication of choice for combatting malaria worldwide. Artemisia annua is known to be efficacious against a range of other diseases, including other tropical maladies and certain cancers, so in our lab we are already at work investigating the effectiveness of DLA with other diseases.”

The results of the case in the Congo have been described in the journal Phytomedicine. You can hear more from Weathers in the video below.

Viagra does more than treat erectile dysfunction. Researchers have found it can slow the spread of malaria.

The little blue pill that gives men more oomph in the bedroom has an unexpected benefit – it can slow the spread of malaria.

Viagra doesn’t just have a stiffening effect on men’s anatomy, it also makes the one-celled parasite that causes malaria more rigid.

A team of European researchers have found that this effect deforms the red blood cells that transport the parasite, encouraging the spleen to clear them from the system.

With fewer infected red blood cells circulating the body, it becomes harder for one of the most common malaria parasites, Plasmodium falciparum, to be transmitted to an uninfected mosquito when it feeds on an infected person or animal.

Lead researcher Catherine Lavasec, from the Pasteur Institute in France, said there was a desperate need for novel interventions to target the transmission of the malaria parasite from a human host to the mosquito.

“Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination,” she said.

Normally, infected blood cells slip by the spleen because they are as squishy as healthy red blood cells.

Using an artificial spleen, the team found that certain drugs such as Viagra, also known as sildenafil, could stiffen these cells by inhibiting an enzyme that would normally make them squishy. The stiff cells are then cleared by the spleen.

As well as treating erectile dysfunction, Viagra has been used to lower blood pressure and relieve altitude sickness.

The research team said their findings are “proof of principle” that certain drugs can target malaria-infected red blood cells and these may be used as a new class of antimalarial drugs.

More than 198 million people were infected with malaria and more than 500,000 people died from the disease in 2013, according to the latest global estimates collected by the World Health Organisation.

The malaria parasite can only be transmitted by the females of certain varieties of mosquitoes from the Anopheles genus. Females need nutrients from a blood meal to develop their eggs.

The study was partly funded by the Bill & Melinda Gates Foundation and the Wellcome Trust and has been published in the scientific journal PLOS Pathogens.

The 10 Ebola treatment centers in West Africa are based on a design of three wards, which help separate patients suspected of having the disease from those with a confirmed diagnosis. Because there are not nearly enough such treatment centers, Liberia and the World Health Organization plan to set up much scaled-down versions, called community care centers, which will provide only rudimentary care. The community care centers would separate suspected and confirmed cases.

1…TriagePatients with symptoms suggesting an Ebola infection are examined in a tent by medical workers wearing protective clothing.

2…Low-probability ward Patients who might not have Ebola wait here for hours or days until tests reveal whether they have the virus.

3…High-probability wardIf the medical staff suspects that someone has Ebola, the person is cared for in this tent until test results are in.

4…Ebola wardConfirmed cases are treated here. Because no cure exists, the medical staff can provide only supportive care, which increases the chance of survival

5…Morgue In some areas, as many as 75 percent of Ebola patients die. Bodies are stored temporar-ily in a morgue until medical workers can bury them

B…Undressing roomWorkers must undress very slowly and carefully to prevent infection, washing hands after removing each item of protective clothing. Some equipment can be reused after disinfection; other items are incinerated.

C…Patient exitRecovered patients take an antiseptic shower, put on clean clothes and step through decontamination basins before leaving the clinic. No longer infec–tious, they carry antibodies against the virus for as many as 10 years

D…Direct entryPatients with clear signs of an Ebola infection are taken straight to the Ebola ward, without going through triage.

E…Cemetery and incinerator Bodies are buried nearby but off site. Medical waste is burned a short distance away from the treatment center.

Virus May Act as ‘Evolution-Proof’

Biopesticide Against Malaria

Science (Aug. 21, 2010) — A naturally occurring virus in mosquitoes may serve as a “late-life-acting” insecticide by killing older adult mosquitoes that are responsible for the bulk of malaria transmission. The researchers from Johns Hopkins University and the Johns Hopkins Malaria Research Institute, Baltimore, Maryland, detail their findings in the August 2010 issue of the Journal of Virology.

Malaria infects hundreds of thousands of people each year and is the cause of over a million deaths worldwide. Insecticides are one of the main strategies currently used to control malaria transmission, however, evolving resistance to such therapies continues to impact such efforts. “Late-life-acting” insecticides (LLAIs) are now being examined as a new approach for controlling malaria as they selectively kill older mosquitoes that spread the disease, while younger mosquitoes survive just long enough to reproduce.

“Reproduction allows for relaxation of evolutionary pressures that select for resistance to the agent,” say the researchers. “If resistance alleles exert fitness costs, there are theoretical scenarios under which resistance is not expected to evolve, leading some to provocatively term LLAIs as ‘evolution-proof’.”

Densonucleosis viruses (or densoviruses [DNVs]) are naturally occurring parvoviruses that have been identified in multiple mosquito species. Some DNVs typically infect during the larval stage and are lethal, however, in this study researchers suggest that the Anopheles gambiae densovirus (AgDNV) may infect at low levels during early life and replicate to lethal levels at adult age. Analysis following infection showed that although AgDNV levels increased modestly during larval development they still replicated slower resulting in significantly decreased virus levels during this stage. Additionally, virus levels greatly increased in 7-to-10-day-old adults.

“Ultimately, we expect that a properly engineered LLAI AgDNV can be deployed in the field to significantly modulate malaria transmission,” say the researchers.